Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin.

Hao Liu,Yunsong Liu,Xiao Zhang,Yongsheng Zhou,Wei Li

doi:10.1186/s13287-015-0195-x

Hao Liu, Yunsong Liu + Show 3 more

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https://doi.org/10.1186/s13287-015-0195-x

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Abstract

IntroductionOsteoporosis is a syndrome of excessive skeletal fragility characterized by the loss of mass and deterioration of microarchitecture in bone. Single use of aspirin or adipose-derived stromal cells (ASCs) has been recognized recently to be effective against osteoporosis. The goal of the study was to evaluate the osteogenic effects of the co-administration of aspirin and allogeneic rat adipose-derived stromal cells (rASCs) on ovariectomized (OVX)-induced bone loss in rats. The underlying mechanisms were investigated in vitro and in vivo.MethodsFirstly, allogeneic rASCs were isolated and cultured, and the conditioned medium (CM) from the maintenance of rASCs was collected. Secondly, the OVX rats were administrated CM, rASCs, aspirin (ASP) or rASCs + ASP, respectively. Twelve weeks later, the anti-inflammatory and osteogenic effects were assessed by micro-CT, undecalcified histological sections, dynamic histomorphometric analyses and serologic assays for biochemical markers. Finally, a Transwell migration assay in vitro and cell-trafficking analyses in vivo were used to explore the effects of aspirin on rASC migration.ResultsSystemic administration of aspirin and rASCs attenuated OVX-induced bone loss better than single use of aspirin or ASCs (p < 0.05, respectively). Next, we analyzed the underlying mechanisms of the anti-inflammatory and chemotactic abilities of aspirin. Aspirin suppressed serum levels of the pro-inflammatory cytokines on tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and the anti-inflammatory ability was positively associated with bone morphometry. Also, aspirin exhibited excellent chemotactic effects in vitro and accelerated the homing of allogeneic rASCs into bone marrow during early in vivo stages.ConclusionsCo-administered aspirin and allogeneic ASCs can partially reverse OVX-induced bone loss in rats. This effect appears to be mediated by the anti-inflammatory and chemotactic abilities of aspirin.

Highlights

Osteoporosis is a syndrome of excessive skeletal fragility characterized by the loss of mass and deterioration of microarchitecture in bone
For bone mineral density (BMD), micro-computed tomography (CT) analyses of the proximal tibia ex vivo demonstrated that the OVX groups (OVX, adipose-derived stromal cells (ASCs) conditioned medium (CM), ASC, ASP, and ASC + ASP groups, n = 50) exhibited significantly less BMD compared with the sham group except the ZOL group (p < 0.001)
Inconsistent with BMD results, the allogeneic rASCs CM (ASC CM) group showed a poor effect upon bone microarchitecture among the treatment groups (ASC CM, ASC, ASP, and ASC + ASP groups)

Summary

Introduction

Osteoporosis is a syndrome of excessive skeletal fragility characterized by the loss of mass and deterioration of microarchitecture in bone. The goal of the study was to evaluate the osteogenic effects of the co-administration of aspirin and allogeneic rat adipose-derived stromal cells (rASCs) on ovariectomized (OVX)-induced bone loss in rats. Osteoporosis is a syndrome of excessive skeletal fragility characterized by loss of the mass and deterioration of the microarchitecture of bone, which leads to fragility fractures [1]. Two major pharmacologic approaches to the treatment of osteoporosis are anabolic agents such as parathyroid hormone [3, 4] (which stimulate bone formation) or antiresorptive agents such as bisphosphonates, calcitonin, raloxifene, and estrogen (which inhibit bone resorption) [5, 6] These therapies have been shown to increase bone mineral density (BMD) and reduce the risk of fractures, but long-term safety and efficacy are ongoing concerns [7]. Obtaining BM is an invasive procedure that can cause complications such as pain, bleeding, and infection

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